# Disease context and longevity genes

> **NIH NIH U19** · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · 2021 · $533,370

## Abstract

ABSTRACT: Disease Context and Longevity Genes Project. Many genetically-mediated factors
contributing to longevity are likely to impact disease processes in addition to some fundamental mechanism of
aging and/or senescence. We believe that an understanding of how much overlap there might be between
genetic variants that impact disease susceptibility, as well as disease-related processes, and genetic variants
that uniquely impact longevity can be obtained by pursuing genetic association studies with large data sets
made up of individuals with different diseases and individuals that have lived an exceptionally long and healthy
life. We will obtain as many relevant data sets with genotype and sequencing data as possible from resources
such as dbGAP and combine them with unique Longevity Consortium (LC) data sets for different types of
analyses. This will lead to unprecedentedly large combined data sets with excellent statistical power, amenable
to either mega (i.e., combined raw data) and meta (i.e., only using summary statistics) data analyses. Relevant
analyses can involve direct association testing or Mendelian Randomization (MR) testing leveraging imputed
intermediate phenotypes for causality analysis, but will have to accommodate a harmonization of phenotypes,
control for population stratification, as well as potential heterogeneity in genetic effects. Tools for dealing with
phenotypic harmonization with be developed and applied, as will analytical methods for handling stratification
and heterogeneity. In fact, the development and implementation of analytical methods that accommodate
heterogeneity will be a main feature of the proposed research. We emphasize that all findings from other LC
investigators will be tested in the proposed analyses, either directly if a genetic variant (e.g., arising from the
Perls-Centenarians project), via orthology for genes arising from the Miller-Mice/Cells project that may
harbor interesting human genetic variants, or via imputation, where possible, as an intermediate phenotype
(e.g., as a protein arising from the Orwoll-Proteomics or metabolite from the Fiehn-Metabolomics projects)
amenable to MR tests. In addition, all factors found to be of interest from the proposed analyses will also be
provided to the other investigators as well as the Price-Systems Biology and Girke-Chemoinformatics
cores for further and integrated analyses. We emphasize that the proposed analyses can be pursued in a wide
variety of ways to yield previously undocumented insights. For example, if diabetes and obesity share genetic
determinants, then combining individuals with diabetes and obesity and comparing them to individuals who
have lived a long life without diabetes or obesity should reveal genetic factors mediating general vulnerabilities
to metabolic diseases in all or a subset of individuals with unprecedented power.

## Key facts

- **NIH application ID:** 10210338
- **Project number:** 5U19AG023122-14
- **Recipient organization:** CALIFORNIA PACIFIC MED CTR RES INSTITUTE
- **Principal Investigator:** NICHOLAS Joseph SCHORK
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $533,370
- **Award type:** 5
- **Project period:** 2004-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210338

## Citation

> US National Institutes of Health, RePORTER application 10210338, Disease context and longevity genes (5U19AG023122-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10210338. Licensed CC0.

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